The efficacy of chemotherapeutic management of cancer depends in part upon the activity of the tumor drug metabolism system since only active antineoplastic agents can combat the growth and metastasis of cancer. Drug metabolism is catalyzed by a membrane-bound multienzyme complex in the endoplasmic reticulum. We propose to characterize the drug metabolism system of selected liver tumors chemically, physically, kinetically, and structurally. We propose to accomplish these goals through purification and reconstitution of the components of the hepatoma drug metabolism system, cytochrome P-450 and cytochrome P-450 reductase. The physical, chemical, and enzymological properties of these purified enzymes will be obtained in order to understand membrane structure and function interrelationships as well as to provide a better base of knowledge for cancer chemotherapy. We will also determine the rate of metabolism of antineoplastic drugs by hepatomas and define the role of the tumor drug metabolism system in the efficacy of chemotherapeutic management of cancer.